Right and left ventricular 24-segment sphericity index is abnormal in small-for-gestational-age fetuses.

OBJECTIVE: Fetuses with growth restriction have been reported to have an abnormal sphericity index (SI), which is indicative of the shape of the ventricular chambers of the heart. Our aim was to evaluate the SI for 24 transverse segments distributed from base to apex of the right (RV) and left (LV) ventricles to determine whether, in small-for-gestational-age (SGA) fetuses, the SI is abnormal at locations other than the basal segment. METHODS: We evaluated 30 SGA fetuses between 25 and 37 weeks of gestation. SI was computed for both ventricles by dividing the end-diastolic mid-basal-apical length by each of 24 end-diastolic transverse segmental widths, from base (Segment 1) to apex (Segment 24). For each ventricle, the Z-score and centile for the SI from each of the 24 segments were computed using the mean and SD from published equations. The 24-segment method, defining abnormal SI as values < 10th centile or > 90th centile, was compared with that of using only the basal segment by chi-square analysis to determine the number of fetuses identified with an abnormal SI. RESULTS: In 23 of the 30 (77%) SGA fetuses, at least one of the 24 transverse segments in one or both ventricles had an abnormal SI; in 17% of cases, both ventricles were affected, in 23% of cases only the RV was involved and in 37% of cases only the LV was involved. Compared with the 24-segment model, significantly fewer fetuses with an abnormal SI were identified using only basal Segment 1, from the RV base (58%, 7/12; P < 0.01) or only Segment 12, in the mid portion of the RV (50%, 6/12; P < 0.005). Combining measurements of Segment 1 and Segment 12 from the RV identified 83% of fetuses with at least one abnormal SI and was not significantly different from using the 24-segment model. Similarly, significantly fewer fetuses with an abnormal SI were identified using only LV basal Segment 1 (63%, 10/16; P < 0.006) or only Segment 12, in the mid portion of the LV (75%, 12/16; P < 0.03), when compared with the 24-segment model. Combining measurements of both LV Segment 1 and Segment 12 identified 81% (13/16) of fetuses with an abnormal SI and was not significantly different from using the 24-segment model. CONCLUSION: The 24-segment SI of RV and LV provides a comprehensive method with which to examine the shape of the ventricular chambers and identifies more SGA fetuses with an abnormal SI than are identified using only the basal segment SI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A new method to assess fetal head descent in labor with transperineal ultrasound.

OBJECTIVES: To assess the feasibility and reproducibility of measuring fetal head station and descent during labor using transperineal ultrasound (TPU) imaging, to compare the evaluation of fetal station through digital examinations with concurrent TPU assessments, and to assess its utility in distinguishing patients whose pregnancy will result in spontaneous vaginal delivery from those who will require operative vaginal delivery or Cesarean section for failure to progress. METHODS: TPU and digital examinations were performed in 88 term laboring patients with a singleton fetus in cephalic presentation. Using TPU imaging, head descent was quantified by measuring the angle between the long axis of the pubic symphysis and a line extending from its most inferior portion tangentially to the fetal skull. Intraobserver and interobserver variability were calculated using variance component analysis. TPU imaging was used to measure the angle of head descent during the second stage of labor in 23 of the women. RESULTS: Analysis of replicated measurements on 75 subjects, by the same observer at approximately the same time, yielded an average SD (intraobserver variability) of approximately 2.9 degrees for the measurement of angle of head descent on TPU examination. A separate variance component analysis on a subset of 15 assessments for which measurements were repeated by a second observer, with two to four replicate measurements obtained by each, yielded an interobserver error estimate of 1.24 degrees. A significant linear association was found between clinical digital assessments and measurement of angle of head descent by TPU examination (P < 0.001). An angle of at least 120 degrees measured during the second stage of labor was always associated with subsequent spontaneous vaginal delivery. In six pregnancies ending in Cesarean section the mean angle of descent measured at last TPU examination was only 108 degrees. CONCLUSIONS: The angle of head descent measured by TPU imaging provides an objective, accurate and reproducible means for assessing descent of the fetal head during labor.

Anatomic relationship between the pubic symphysis and ischial spines and its clinical significance in the assessment of fetal head engagement and station during labor.

OBJECTIVE: To develop a geometric model from computed tomographic (CT) images in non-pregnant women that would objectively reflect clinical head station in laboring patients, against which to test the accuracy of digital examinations. METHOD: CT scans were performed in 70 non-pregnant women to determine, using a geometric model, which angle in a mid-sagittal transperineal ultrasound (TPU) image best coincided with the mid-point of a line drawn between the ischial spines (zero station). Using a geometric algorithm, TPU angles were then assigned for other clinical stations (-5 to + 5). Finally, clinical station was assessed by digital examination and simultaneous TPU assessments in 88 laboring patients to see how closely the clinical examination correlated with the station calculated from the above geometric model. RESULTS: The mean angle between the long axis of the symphysis pubis and the mid-point of the line connecting the two ischial spines for the 70 non-pregnant subjects was 99 degrees . The geometric model developed allowed us to build an algorithm to assign a specific set of theoretical angles to each computed station. Relationships between digitally assessed fetal head station, TPU angle for each station, and the geometrical model created with CT data, are reported. Clinical digital assessment of station correlated poorly with computed station, especially at stations below zero, where it could have greater clinical impact. CONCLUSION: The TPU angle of 99 degrees correlated with zero station, and each station above or below this station could be assigned a specific corresponding angle for reference.

The relationship of fetal eye movements to non-stress test results.

OBJECTIVE: This study was designed to correlate ultrasound-observed fetal eye movements with fetal heart rate reactivity to determine its potential role in fetuses with persistent non-reactivity. METHODS: A total of 104 non-stress tests (NSTs) were evaluated in 62 patients referred for fetal surveillance for standard antepartum indications. Ultrasound-observed eye movements, assessed during portions of these NSTs, were categorized as negative (0), intermittent (1-5/min), or rapid (> or = 6/min). RESULTS: Of the NSTs, 97 were reactive and seven were non-reactive. All studied fetuses were apparently healthy, as the seven patients with persistently non-reactive NSTs had biophysical profile scores of 8/10. During the NSTs, 120 reactive portions and 81 non-reactive portions were evaluated for ultrasound-observed eye movements. During reactive portions, eye movements were negative 19% of the time, intermittent 24% of the time and rapid 56% of the time. During non-reactive portions, eye movements were negative 84% of the time, intermittent 7.8% of the time and rapid 7.8% of the time. All fetuses demonstrating eye movements during non-reactive periods became reactive shortly thereafter, and all of the seven persistently non-reactive fetuses displayed negative ultrasound-observed eye movements throughout the entire observation period. CONCLUSIONS: Healthy fetuses display a strong relationship between non-reactive heart rate tracings and absent or diminished eye movements, consistent with quiet sleep. Conversely, reactive periods are associated with a high incidence of rapid eye movement. Further study is needed in fetuses documented to be hypoxic.

Reduction of subcutaneous mass, but not lean mass, in normal fetuses in Denver, Colorado.

OBJECTIVE: To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. STUDY DESIGN: Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. RESULTS: Gestational age at delivery was similar between groups. Birth weight was less at Denver's altitude (2991 +/- 79 g versus 3247 +/- 96 g; P =.04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver's altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. CONCLUSIONS: The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations.

In utero gene delivery by intraamniotic injection of a retroviral vector producer cell line in a nonhuman primate model.

In utero gene therapy (IUGT) offers the promise of treating a wide variety of genetic diseases before the development of disease manifestations. The most convenient and potentially easiest method of targeting the fetus is through injection into the amniotic cavity. For long-term correction of genetic defects, retroviral vectors have great potential as a tool for gene therapy strategies. However, retroviral vectors are limited by growth to low titers. In an attempt to increase the amount of vector particles delivered and assess the potential of intraamniotic administration, we injected a retroviral vector producer cell line encoding the lacZ gene into the amniotic fluid of a nonhuman primate model. After birth the infants were analyzed for vector-mediated transduction. Two of four fetuses were successfully transduced, with transgene expression detected in the esophagus, trachea, and stomach. In some sections of tissue, nearly 100% of the cells lining the lumen of these tissues were positive for transduction. Although successful, the limited number of tissues in which transduction was observed led to an in vitro analysis of the effects of amniotic fluid (AF). The presence of amniotic fluid inhibited transduction by 99%. AF affected both the transducing activity of the vector and the health of the packaging cells. The negative effects of AF were gestational age dependent; greater inhibition was observed from AF collected at later stages of pregnancy. The fact that transduction was successful despite these negative effects indicates that this approach is a promising strategy for gene therapy.

The impact of prenatal alcohol exposure on frontal cortex development in utero.

OBJECTIVE: Whether prenatal alcohol exposure was associated with a reduction in the frontal cortex was examined. STUDY DESIGN: Pregnant women (n = 167) received multiple ultrasonographic assessments. During the assessment, brain structures were visualized and measured, including the distance from the posterior margin of the cavum to the calvarium, the distance from the posterior margin of the thalamus to the calvarium, the transcerebellar diameter, and the biparietal diameter. RESULTS: Regression analyses and odds ratios demonstrated that alcohol exposure was associated with a reduction in the frontal cortex, but not other brain structures. Strikingly, the percent of fetuses with a frontal cortex below the 10th percentile increased from 4% for nonexposed fetuses to 23% for heavily exposed fetuses. CONCLUSION: There was a relationship between frontal brain size and maternal alcohol consumption, suggesting that ultrasonography may be a sensitive tool for detecting alcohol-induced changes in the fetal brain.

First trimester prenatal diagnosis of chondroectodermal dysplasia (Ellis-van Creveld syndrome) with ultrasound.

Chondroectodermal dysplasia (Ellis-van Creveld syndrome) is an autosomal recessive condition characterized by short-limb dwarfism, postaxial polydactyly, ectodermal defects, and congenital heart disease. This condition is most prevalent in the Amish population of Lancaster, Pennsylvania, USA, occurring in 1/5000 births and in 1/60,000 births in the general population. This report presents a case of ultrasonographic detection of chondroectodermal dysplasia at 12 weeks of gestation.

Comparison of low- and high-altitude Doppler velocimetry in the peripheral and central circulations of normal fetuses.

OBJECTIVE: Our aim was to test the hypothesis that Doppler velocimetry of the peripheral and central circulations in normal fetuses is not affected by moderately high altitude (Denver, Colo-1609 m) compared with sea level (Milan, Italy-40 m). STUDY DESIGN: One hundred nineteen patients with singleton pregnancies underwent Doppler waveform analysis of the following: umbilical artery, uterine artery, middle cerebral artery, ductus venosus, and the tricuspid and mitral valves. RESULTS: Birth weights were reduced at Denver's altitude (P<.001). The early/late diastolic inflow ratios of the atrioventricular valves increased with gestational age (P<.01), whereas systolic/diastolic ratios of the uterine and umbilical arteries decreased with gestational age (P<.01). There were no Doppler velocimetry differences in any vessel between Denver's and Milan's altitudes. CONCLUSIONS: Gestational age has the same effect on Doppler index at both high and low altitudes. Moderately high altitude does not affect uteroplacental or fetal vascular Doppler index and may reflect normal acclimatization in the smaller Denver fetuses.

Striking findings concerning the variability in the measurement of the fetal renal collecting system.

OBJECTIVE: Using strict thresholds of normality, investigators have reported associations between fetal pyelectasis and aneuploidy, obstructive uropathy, postnatal pyeloplasty and vesicoureteral reflux. Although evidence continues to mount regarding the importance of fetal pyelectasis, little is known of the variability of collecting system measurements. To investigate the short-term variability and its relationship to bladder dilatation, the following study was conducted. DESIGN: During May and June 1996, 20 mid- and late-trimester patients with varying degrees of fetal pyelectasis were recruited into this study. Each consented to undergo periodic (every 15 min for 2 h) ultrasound measurements of the fetal renal collecting systems and bladder. To account for anatomic and technical variability in measurement, we used both the sum of the transverse and anterior-posterior (AP) measurements of the collecting systems, and AP measurement alone for comparison. The variability of the collecting system measurements was assessed based upon gestational age, magnitude of pyelectasis and fetal bladder size. RESULTS: We investigated 38 renal units in 20 patients (eight in the second trimester and 12 in the third). The mean(SE) AP diameter of all kidneys was 5.89(2.49) mm (range 15 (2-17) mm), and the sum of transverse and AP renal collecting system diameters was 13.91(5.73) mm (range 26 (4-31) mm). These data were normally distributed. When assessing the variability in individual kidneys over time, we found the mean variation (minimum to maximum) for the sum of the AP and transverse measurement to be 7.61(4.26) mm and for the AP measurement alone to be 3.80(2.49) mm. No relationship was found between variability of dilatation, magnitude of dilatation or fetal bladder size. Cyclic dilatation of the fetal bladder was observed in all cases. The mean time from maximal to minimal dilatation was 20 min (1.34 observations; range 12-30 min). CONCLUSIONS: We found the size of the fetal renal collecting system to be highly variable over the course of a 2-h period. Seventy per cent of cases (14 of 20) had both normal (< 4 mm) and abnormal values (> or = 4 mm) during the 2-h study period. Significant caution should be used when considering the implications of renal collecting system dilatation based upon a single AP measurement.

Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group.

OBJECTIVES: Patients admitted with an acute episode of preterm labor who respond to early intravenously administered tocolysis remain at risk of having subsequent episodes of preterm labor and preterm delivery. Several pharmacologic agents have been used in an attempt to reduce subsequent episodes of preterm labor, and all are associated with significant side effects. Atosiban, an oxytocin receptor antagonist, is effective in the treatment of an acute episode of preterm labor. This study was designed to compare the efficacy and safety of atosiban with those of placebo maintenance therapy in women with preterm labor who achieved uterine quiescence with intravenous atosiban. STUDY DESIGN: A multicenter, double-blind, placebo-controlled trial was designed for patients in preterm labor who responded to early intravenous treatment with atosiban. Five hundred thirteen patients were randomly assigned to receive maintenance therapy, 252 to receive atosiban, and 251 to receive matching placebo. Maintenance therapy was administered as a continuous subcutaneous infusion, via pump, of 30 microg/min to the end of 36 weeks' gestation. The primary end point was the number of days from the start of maintenance therapy until the first recurrence of labor. A secondary end point was the percentage of patients receiving subsequent intravenous atosiban therapy. RESULTS: The time (median) from the start of maintenance treatment to the first recurrence of labor was 32.6 days with atosiban and 27.6 days with placebo (P =.02). At least one subsequent intravenous atosiban treatment was needed by 61 atosiban patients (23%) and 77 placebo patients (31%). Except for injection site reactions, adverse event profiles of atosiban and placebo were comparable. There were 4 neonatal deaths reported in the atosiban group and 5 in the placebo group after the start of maintenance therapy. Infant outcomes (including birth weight) were comparable between maintenance and treatment groups. CONCLUSIONS: Maintenance therapy with the oxytocin receptor antagonist atosiban can prolong uterine quiescence after successful treatment of an acute episode of preterm labor with atosiban. Treatment was well tolerated.

Skeletal anomalies.

It is possible to identify many types of skeletal dysplasias and conditions involving limb deformities prenatally using ultrasound. It is likely that in the future, with the advancing technology and discoveries in molecular genetics, specific mutation analysis will become available for many of these conditions. This will make first trimester diagnosis an option in many cases. Because of the complex nature of many of these cases, it may be helpful to use a multidisciplinary approach involving a radiologist and a geneticist at times. In utero radiographs may help clarify a diagnosis. In lethal cases where a specific diagnosis has not been confirmed, it may be helpful postpartum to obtain an autopsy; photographs; complete body radiographs; karyotypic analysis; and specimens of bone, cartilage, and fetal blood for further analysis.

Umbilical vein blood flow determination in the ovine fetus: comparison of Doppler ultrasonographic and steady-state diffusion techniques.

OBJECTIVE: This study was undertaken to assess the accuracy of triplex ultrasonographic measurement of venous umbilical blood flow in comparison with the steady-state diffusion technique and to determine the impact of cotyledon weight and number on umbilical blood flow. STUDY DESIGN: Six late-gestation ewes with long-term catheter placement were studied for venous umbilical blood flow with the ethanol steady-state diffusion technique and with triplex-mode ultrasonography (color Doppler, pulsed-wave Doppler, and real-time ultrasonography). At necropsy the number and weight of the cotyledons serving each umbilical vein were recorded. RESULTS: Umbilical blood flow determined by triplex-mode ultrasonography (207. 5 +/- 8.6 mL. kg(-1) fetus. min(-1)) was virtually identical to that determined with the steady-state diffusion technique (208.1 +/- 7.3 mL. kg(-1) fetus. min(-1); P =.9). When values were normalized for the weight or number of cotyledons serving each vein, there was no difference in umbilical blood flow between small and large umbilical veins in all the sheep. CONCLUSIONS: Our study validates the accuracy of the triplex ultrasonographic method and provides justification for its use in future human investigations. In absolute terms umbilical blood flow frequently differs between the 2 veins. When expressed per number or mass of cotyledons, however, the umbilical blood flows are similar.

Measuring disability and outcomes in routine practice with the FACE Core Assessment.

The authors describe the results of an outcome study of 87 psychiatric inpatients and outpatients using a generic assessment and outcome measurement tool, the FACE Core Assessment. The results suggest that the multiaxial structure of the assessment tool has the potential to be used for the routine measurement of clinical outcomes as well as for multidisciplinary assessment.

Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency.

OBJECTIVE: Intrauterine growth restriction in an ovine model occurs after exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether intrauterine growth restriction is reversible on removal of the heat stress after only 55 days of exposure; that is, does a brief exposure at a critical point of development suffice? STUDY DESIGN: Five pregnant ewes were exposed to heat stress beginning at 35 days' gestation and were removed after 55 days of exposure. Five ewes in a control group were studied as contemporaneous controls and added to data from 37 ewes in a control group previously studied. Serial fetal biometric ultrasonographic measurements (biparietal diameter, abdominal circumference, femur length, and tibia length) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter, and comparisons were made between fetuses in the group exposed to heat stress for 55 days and 42 fetuses in the control group and 4 fetuses from a previous study that were exposed to heat for 80 days. Regression lines, 95% confidence intervals, and slopes were determined for each study group. RESULTS: Both the 55-day and the 80-day heat exposure groups showed a significant reduction in fetal and placental weights compared with the control group. Animals in the 80-day group had significantly lower fetal and placental weights than the animals in the 55-day group (P <.05). Indexes of somatic growth (abdominal circumference, femur length, and tibia length) for the control group were significantly greater than those of either the 55-day group or the 80-day group (P <.001). Asymmetric growth restriction was evident in both heat groups by a biparietal diameter/abdominal circumference ratio that was significantly higher than in the control group (P <.004 for the 55-day group and P <.001 for the 80-day group). The slopes for somatic parameters (abdominal circumference, femur length, and tibia length) versus time became significantly different between the control and 55-day groups at 77, 101, and 80 days' gestation, respectively. The 55-day group had abdominal circumference and femur length measurements that were significantly greater than those in the 80-day group. CONCLUSION: The fetuses in the 55-day and 80-day groups reflect a pattern of asymmetric intrauterine growth restriction. Our findings suggest that the initial insult affecting fetal and placental growth occurs early in gestation, but removal of fetuses after only 55 days of exposure significantly reduces the degree of fetal growth restriction compared with that found in those fetuses exposed for 80 days.

Microchimerism and tolerance following intrauterine transplantation and transfusion for alpha-thalassemia-1.

A fetus homozygous for alpha-thalassemia-1 was given haploidentical paternal CD34 cells at 13, 19 and 24 weeks' gestation and supported through pregnancy by blood transfusion. The fetal hematocrit ranged between 27 and 47% and between one half and three quarters of this hemoglobin was of recipient (Bart's) type. Intrauterine growth proceeded normally and no significant fetal hydrops was detected. Tests for donor HLA antigens, and alpha-globin DNA, were negative on fetal blood samples drawn before birth. A positive signal for alpha-globin DNA was obtained from cord blood and from marrow obtained at 3 months of age, suggesting that some donor stem cells had persisted in the recipient. The infant's blood mononuclear cells showed little proliferative and no cytotoxic response to the donor while responses to a third party were present. Additional paternal CD34 cells given at 3 months age did not reduce transfusion dependency in the subsequent 6 months. Our results show that repeated transfusions can support an alpha-thalassemia-1 fetus through pregnancy, in this instance without significant birth defects or apparent hypoxic tissue injury. The donor stem cells did not have a survival advantage compared with endogenous stem cells, but appeared to survive in the recipient as judged by the persistence of an alpha-globin DNA signal. In vitro studies of alloreactivity suggest tolerization of the host to the donor's MHC disparity. Future efforts will focus on exploiting this tolerance to improve the level of donor chimerism.

Doppler velocimetry of growth-restricted fetuses in an ovine model of placental insufficiency.

OBJECTIVE: With an ovine model in which growth restriction was induced by exposure to heat stress, our aims were as follows: (1) to describe the normal gestational age-related changes in Doppler velocimetry in the ovine fetal aorta and umbilical artery and (2) to compare Doppler velocimetry between heat-stressed and non-heat-stressed fetuses. STUDY DESIGN: Five ewes were exposed to heat stress for 55 days beginning at 35 days' gestation. Five ewes were not exposed and served as controls. Aortic and umbilical artery pulsed Doppler velocimetry was obtained, including the systolic/diastolic ratio, pulsatility index, and resistance index. Data were obtained between 50 and 120 days' gestation. Linear regression analysis was used to analyze gestational age-related changes in velocimetry. Comparison of mean index values between heat-stressed and non-heat-stressed fetuses were made with analysis of variance. RESULTS: Heat-stressed fetuses demonstrated significantly higher systolic/diastolic ratios and pulsatility index values for both umbilical artery (p < 0.025; p < 0.033) and aorta (p < 0.017; p < 0.022) compared with controls. The umbilical artery and aortic resistance index values were not different between groups (p < 0.079; p < 0.28). The slopes for each of the Doppler index values were negative in both normal and heat-stressed fetuses. Umbilical artery and aortic end-diastolic flows remained absent through the first 70 days of gestation in both groups. CONCLUSION: Doppler velocimetry index values decrease with increasing gestational age, reflecting decreased placental bed vascular resistance. The higher Doppler index values seen in the heat-stressed group are consistent with increased placental vascular resistance. The normal absence of diastolic flow until 70 days' gestation is similar to the pattern described in humans.

Morphometry of fetal growth.

Intrauterine growth retardation (IUGR) complicates about 5% of all pregnancies and is responsible for substantial perinatal mortality and morbidity. With ultrasound, it is possible to assess fetal brain growth indirectly by measurement of the biparietal diameter, head circumference and transcerebellar diameter. As liver size is affected most profoundly by IUGR, measurement of the abdominal circumference of the fetus provides the earliest evidence of fetal growth restriction. Placental size, assessed with ultrasound, can also indicate the severity of the condition. Once a fetus is diagnosed as having IUGR, its well-being can be monitored with standard heart-rate testing and ultrasound assessment of fetal behaviour. Doppler analysis of the wave form of the fetal arterial and venous circulation hold the greatest promise for managing pregnancies complicated by IUGR.